Biomedical subjects

P Wilton

Publications and source records attributed to P Wilton.

At least 19 recordsLinked to original sources

PubMed2006

Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database.

OBJECTIVE: To test the hypothesis whether the effects of GH replacement therapy in adults could be affected by prior pituitary irradiation, the baseline characteristics and response to GH were evaluated in adults with severe GH deficiency (GHD), who had received or not irradiation for the treatment of pituitary adenoma or craniopharyngioma. DESIGN: Data from 447 patients, who had received radiotherapy (427 in addition to surgery), and 630 patients, who were operated on but not irradiated for their tumour, were retrieved from Pfizer International Metabolic Database (KIMS) and compared at baseline and 1 and 2 years following the onset of GH replacement. RESULTS: Irradiated and non-irradiated patients exhibited the expected phenotype of GHD at baseline. However, irradiated patients had a greater impairment in the quality of life (QoL), a higher fat mass, lower high-density lipoprotein cholesterol levels and a lower bone mineral content (BMC) than non-irradiated patients. Treatment with GH induced similar changes in both groups. After 1 year of GH replacement, there was an increase in serum IGF-I and fat-free mass, a reduction in fat mass and an improvement in QoL, all changes being equivalent in irradiated and non-irradiated patients. The lipid profile also improved with the irradiated patients showing a better response. These beneficial effects were maintained and the BMC also increased in both groups by the second year of treatment. CONCLUSIONS: This analysis shows that prior irradiation for pituitary adenoma or craniopharyngioma does not compromise the beneficial effects of GH replacement therapy.

Adenoma↗

PubMed2002

Devolved budgetary responsibility in primary care. A cross-country assessment of the impact on efficiency.

General Practitioners and primary care physicians have a pivotal role in the allocation of health care resources in most countries. With increasing costs of care, they have therefore become a significant focus for healthcare reform in the pursuit of increased efficiency. For example, the United Kingdom (UK), United States of America (USA), New Zealand (NZ), Germany and The Netherlands, have all pursued reforms introducing explicit budgetary responsibilities for primary care. While there is a common set of objectives underlying such budgetary responsibilities, different versions have been introduced to reflect specific health environments. As most of these reforms were introduced in the early to middle 1990s, it is timely to examine their impact on efficiency. This paper therefore provides an econometric assessment of the effect of budgetary arrangements in the UK, USA, NZ, Germany and The Netherlands on the growth of primary care expenditure and flow-on costs (as proxied by pharmaceutical expenditure), as proxy indicators for efficiency. The results suggest that for all countries there is some support for efficiency improvements through the implementation of budgets for primary care.

Journal Article↗

PubMed2002

Normal progression of testicular size in boys with idiopathic short stature and isolated growth hormone deficiency treated with growth hormone: experience from the KIGS.

BACKGROUND: The aim of this retrospective analysis was to evaluate the effects of growth hormone (GH) treatment on testicular development in boys with idiopathic short stature (ISS) and isolated GH deficiency (IGHD) followed in the KIGS (Pharmacia International Growth Database). METHODS: For inclusion in the study, the patients had to have received more than 1 year of prepubertal GH treatment, at least 4 consecutive years of GH treatment in total, and to have attained their final height, defined as a height velocity of less than 2 cm/year. Data on 107 boys in the KIGS database have been analyzed. RESULTS: No significant differences in duration of GH treatment and testicular volume at the start of treatment or at final height were found between the boys with ISS and those with IGHD. The progression of testicular volume in boys with ISS or IGHD during GH treatment did not differ from the reference population. CONCLUSIONS: This analysis shows that GH treatment does not alter testicular growth in boys with ISS or IGHD. However, prospective controlled studies are needed to rule out moderate attenuating or stimulating effects.

Adolescent↗

PubMed2001

Short stature in Noonan syndrome: response to growth hormone therapy.

BACKGROUND: Growth hormone (GH) has been used to promote growth in both the short and long term in a number of dysmorphic syndromes, including Turner syndrome. As this condition shares many clinical features with Noonan syndrome, it would seem logical to treat the latter group with GH. AIMS: To assess the short and long term response to GH therapy in patients with Noonan syndrome. METHODS: Analysis of patients with Noonan syndrome in the Pharmacia & Upjohn International Growth Study (this post-marketing database contains data on the majority of patients currently treated with GH in the UK). A questionnaire was also sent to participating clinicians. RESULTS: Data on 66 patients (54 males) were available for study. At the start of GH therapy children were short, compared with both normal and Noonan children. During the first year of GH therapy height velocity increased from a mean of 4.9 to 7.2 cm per year. For patients treated long term with GH, mean height SDS increased from -2.9 pretreatment to -2.6 after one year and -2.3 after five years. Of the 10 patients at near final height, only one had a height above the 3rd centile for normal adults and above the mean for untreated Noonan patients. The mean increment in final height was 3.1 cm (range -1.1 to 6.5 cm). CONCLUSIONS: GH therapy in patients with Noonan syndrome will improve height velocity in the short term. Longer-term therapy results in a waning of effect; initial indications are that final height is not improved substantially in most patients.

Adolescent↗

PubMed2001

The potential of prediction models based on data from KIGS as tools to measure responsiveness to growth hormone. Pharmacia International Growth Database.

Various prediction models have been developed, based on data documented within KIGS (Pharmacia International Growth Database), for use in the growth hormone (GH) treatment of children with short stature resulting from GH deficiency (GHD) or other causes. In addition to the practical value of such models as part of a 'forward strategy' guiding GH treatment, we now propose that prediction models may also be useful for the identification of individual variance in responsiveness. In a comparison involving 1,800 children with idiopathic GHD (IGHD), 151 children who acquired GHD after treatment for medulloblastoma and 192 children with GHD accompanying craniopharyngioma, it was shown that the responsiveness to GH of patients with craniopharyngioma equalled that of IGHD patients, whereas patients with medulloblastoma were less responsive. These observations and the identification of 'good' and 'poor' responders to GH have practical clinical consequences (e.g. modification of treatment), and will, in the future, lead to the identification of those factors which determine the variability of sensitivity to GH. This will improve the efficacy and safety of GH treatment as well as reducing the costs involved.

Databases as Topic↗

PubMed2001

Safety in growth hormone replacement therapy: a matter of varied responsiveness?

Many studies of dosing and pharmacokinetics in growth hormone (GH) replacement therapy have been conducted, whereas there have been few studies examining GH sensitivity and individual responses to GH. It is probable that sensitivity to GH in terms of beneficial effects will be different from sensitivity in terms of fluid retention. Several factors, including age, body mass index and GH-binding protein levels have been implicated in growth and metabolic responses to GH in children and adults, respectively. Fluid retention during GH replacement in adults has been linked to age, body mass and body mass index. These conclusions are broadly supported by data from KIMS (Pharmacia International Metabolic Database), which also show that women are more susceptible than men to symptoms of fluid retention during GH replacement. Very few children undergoing GH therapy experience fluid retention, and thus it is difficult to draw conclusions about sensitivity. In the future, multiple regression analysis may be a useful tool for fully understanding the factors involved in individual responses to GH replacement.

Adult↗

PubMed2001

Healthcare consumption decreases in parallel with improvements in quality of life during GH replacement in hypopituitary adults with GH deficiency.

The morbidity associated with GH deficiency (GHD) in adults is now well established. Furthermore, many controlled clinical trials have demonstrated the efficacy of GH replacement therapy. The aim of the present study was to determine whether the effects of GH replacement in adults are reflected in a reduced use of healthcare resources, in addition to improving quality of life (QoL). Data concerning visits to the doctor, number of days in hospital, and amount of sick leave were obtained from patients included in KIMS (Pharmacia International Metabolic Database), a large pharmacoepidemiological survey of hypopituitary adults with GHD, for 6 months before GH treatment and for 6-12 months after the start of treatment. Assistance required with normal daily activities was recorded at baseline and after 12 months of GH therapy. QoL (assessed using a disease-specific questionnaire, QoL-Assessment of GHD in Adults) and satisfaction with physical activity during leisure time were also assessed. For the total group (n = 304), visits to the doctor, number of days in hospital, and amount of sick leave decreased significantly (P < 0.05) after 12 months of GH therapy. Patients also needed less assistance with daily activities, although this was significant (P < 0.01) only for the men. QoL improved after 12 months of GH treatment (P < 0.001), and both the amount of physical activity and the patients' satisfaction with their level of physical activity improved after 12 months (P < 0.001). In conclusion, GH replacement therapy, in previously untreated adults with GHD, produces significant decreases in the use of healthcare resources, which are correlated with improvements in QoL.

Epidemiologic Methods↗

PubMed2001

The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. .

To assess the influence of factors affecting fracture risk and bone density in adult hypopituitary patients with growth hormone deficiency (GHD), data from a large-scale pharmacoepidemiological survey (the Pharmacia & Upjohn International Metabolic Database [KIMS]) were analyzed and compared with data from a control population (the European Vertebral Osteoporosis Study [EVOS]). The KIMS group consisted of 2084 patients (1112 men and 972 women) with various types of pituitary disease and EVOS consisted of 1176 individuals (581 men and 595 women). Fracture and bone mineral density (BMD) data were available from 2024 patients from the KIMS group and 392 patients from EVOS. The prevalence of fractures in patients with hypopituitarism was 2.66 times that in the non-GH-deficient EVOS population. Adult-onset hypopituitarism with GHD was associated with a higher fracture risk than childhood-onset disease, and patients with isolated GHD had a similar prevalence of fractures to those with multiple pituitary hormone deficiencies. Hormonal replacement therapy with L-thyroxine, glucocorticoids, and sex steroids did not affect the risk of fracture in KIMS patients. In addition, fracture rates in KIMS were independent of body mass index (BMI) and the country of origin. However, smoking was associated with a higher fracture rate in this group. In summary, this is the first large-scale analysis to support the hypothesis of an increased fracture risk in adult patients with hypopituitarism and GHD. This increased risk appears to be attributable to GHD alone, rather than to other pituitary hormone deficiencies or to their replacement therapy.

Age of Onset↗

PubMed2001

Directly observed treatment for multidrug-resistant tuberculosis: an economic evaluation in the United States of America and South Africa.

OBJECTIVE: To estimate the cost-effectiveness of directly observed treatment compared to conventional therapy in reducing the spread of multidrug-resistant tuberculosis, for an industrialised country (represented by the United States of America) and a developing country (South Africa). METHODS: Monte Carlo analysis using published data on probability, cost and health impact. RESULTS: In both countries, directly observed treatment is the dominant strategy, yielding cost savings and improved health outcomes. Cost savings for directly observed treatment relative to conventional therapy become more significant as more expensive second-line drugs are used in treatments. CONCLUSIONS: The cost-effectiveness of directly observed treatment relative to conventional therapy is demonstrated for both the USA and South Africa. Cost savings are more pronounced (especially for South Africa) as the likelihood of multidrug-resistant tuberculosis increases and more expensive second-line therapies are used. Given that health care resources are more severely constrained in developing countries, the data contained in this study are useful in guiding the design of policies for the effective management of multidrug-resistant tuberculosis in settings with limited resources.

Antitubercular Agents↗

PubMed2000

Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment.

BACKGROUND: Growth hormone (GH) contributes to insulin resistance, but whether children treated with GH are at increased risk of diabetes has not been established. We undertook a retrospective analysis of data from an international pharmacoepidemiological survey of children treated with GH to find out the incidence of impaired glucose tolerance and types 1 and 2 diabetes mellitus. METHODS: Reports to the survey of abnormal glucose metabolism were investigated and classified. The incidence and age-distribution of type 1 diabetes were compared with values from a model of reference data. The incidence of type 2 diabetes was compared with data from two reports of children not treated with GH. FINDINGS: 85 (0.36%) of 23333 children were reported with abnormal glucose metabolism. After investigation, 43 had confirmed glucose disorders (11 with type 1 diabetes, 18 with type 2 diabetes, and 14 with impaired glucose tolerance). The incidence and age at diagnosis of type 1 diabetes in children treated with GH did not differ from expected values. The incidence of type 2 diabetes was 34.4 cases per 100000 years of GH treatment which was six-fold higher than reported in children not treated with GH. Type 2 diabetes did not resolve after GH therapy was stopped. INTERPRETATION: GH treatment did not affect the incidence of type 1 diabetes mellitus in any age group. We postulate that the higher than expected incidence of type 2 diabetes mellitus with GH treatment may be an acceleration of the disorder in predisposed individuals.

Adolescent↗

PubMed2000

Growth hormone deficiency and replacement in elderly hypopituitary adults. KIMS Study Group and the KIMS International Board. Pharmacia and Upjohn International Metabolic Database.

OBJECTIVE: Although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of growth hormone (GH) responsiveness on dynamic testing, there are few data available on response to GH replacement. The objective of this study was to compare the baseline characteristics and longitudinal response to GH replacement in patients aged > 65 years with that observed in younger patients enrolled in KIMS (Pharmacia and Upjohn International Metabolic Database). KIMS is a physician-managed, open, long-term surveillance study of adult GH-deficient patients receiving GH replacement. Patients were entered and data provided by interested physicians. PATIENTS: Baseline characteristics were studied in 109 patients (66 males) aged > 65 years commencing GH replacement at time of entry into KIMS and the effects of GH replacement on blood pressure, lipids and quality of life in 64 patients who had completed at least 6 months of GH replacement. Data were compared with baseline data on 863 patients aged < 65 years with adult onset GH deficiency, who had not received GH for at least 6 months prior to entry into KIMS, 220 of whom went on to complete > 6 months GH therapy in KIMS. RESULTS: Blood pressure, cholesterol and LDL cholesterol were positively correlated with age, particularly in females, and older patients had a predictably higher prevalence of diabetes mellitus and history of hypertension. The frequency of previous fractures was increased in females but not in males aged > 65 years. Body mass index, waist/hip ratio and quality of life (AGHDA score) was similar in both groups prior to commencement of GH therapy. GH replacement doses were similar in younger and older patients and the percentage of patients with serum IGF-I of > 2SD above the age-related normal mean was not significantly different between the groups (< 65 years, 20%; > 65 years, 11%). After 6 months of GH replacement significant improvements were evident in waist circumference, waist/hip ratio, diastolic blood pressure, total and LDL cholesterol and AGHDA score in patients aged < 65 years. Similar significant reductions in total and LDL cholesterol were evident in patients > 65 years. In addition, male patients aged > 65 years demonstrated significant reductions in diastolic blood pressure and AGHDA score but no change in waist circumference whereas females aged > 65 years demonstrated a trend to reduction in waist circumference and AGHDA score. CONCLUSIONS: These data, derived from the largest series of GH-treated hypopituitary patients published to date, confirm similar baseline characteristics and positive benefit from GH replacement in older compared with younger hypopituitary patients particularly in relation to quality of life.

Aged↗

PubMed2000

Growth hormone and neurofibromatosis.

Data collected from 102 neurofibromatosis (NF) children with growth hormone (GH) deficiency (GHD) who were receiving GH replacement therapy were reviewed to assess the efficacy and safety of GH therapy in this condition. GH was administered at a mean dose of 0. 18 mg/kg/week. During the 1st year the median height velocity increased significantly from 4.2 cm/year before treatment to 7.1 cm/year, and the median height standard deviation score increased from -2.4 to -1.9. The response to therapy, however, was not as good as that observed in patients with idiopathic GHD. GH therapy did not influence the progression of any of the features of NF, including intracranial tumours, and was not associated with an excess of other adverse events. We conclude that GH treatment of NF patients with GHD is beneficial in terms of improved growth rate and is well tolerated.

Adolescent↗

PubMed2000

Prediction of long-term response to recombinant human growth hormone in Turner syndrome: development and validation of mathematical models. KIGS International Board. Kabi International Growth Study.

It has become common practice to apply GH treatment in short Turner syndrome patients with the objective of promoting growth. The variability in response and the high costs of this treatment demand the individualization and optimization of therapy. Based on 686 prepubertal Turner patients from the Kabi International Growth Study (KIGS; Pharmacia & Upjohn, Inc. International Growth Database), we undertook a multiple regression analysis of height velocity (centimeters per yr) by using various parameters of potential relevance. Derived prediction models for the first 4 yr of GH treatment were validated with 76 additional KIGS patients and 81 patients from Tuebingen, Germany. Among the 6 predictors identified, the most influential variable for first year growth response was the natural log (ln) of the weekly GH dose. The first year growth response was also correlated with age and distance between height and target height (SD score; both negative) and body weight SD, number of GH injections per week, and oxandrolone treatment given additionally (positive). The first year model explains 46% of the variability, with 1 SD of 1.26 cm. For the second to fourth years, 5 predictors were identified: height velocity during previous years, weekly GH dose (ln), weight SD, oxandrolone therapy (all positive), and age (negative). These models explained 32%, 29%, and 30% of the variability, respectively, with SD scores of 1.1, 1.0, and 1.0 cm, respectively. When the models were applied to the other cohorts, no significant difference was noted between observed and predicted responses. Although the parameters used in our models do not entirely explain the variability in the growth response in Turner syndrome, the parameters themselves were clinically relevant to our present understanding and proved to be of high precision. Some of the tested markers, such as karyotype, do not contribute to the growth response. These variables make the models practical and suitable for planning beneficial and cost-effective therapy.

Anabolic Agents↗

PubMed1999

GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety.

OBJECTIVE: Long-term experience of growth hormone (GH) replacement therapy in a large population of hypopituitary adults with GH deficiency (GHD) is limited, and safety surveillance is clearly essential. KIMS, the Pharmacia & Upjohn International Metabolic Database, is a long-term, open, outcomes research programme of hypopituitary adult patients with GHD who are treated in a conventional clinical setting. PATIENTS: The present analysis encompasses data from 1034 hypopituitary adult GHD patients treated with GH for a total of 818 patient years. RESULTS: Prior to GH therapy, the KIMS patient population exhibited an increased prevalence of obesity, diabetes mellitus (in females) and hyperlipidaemia, compared with normal populations described in published studies. Quality of life, assessed using a disease-specific questionnaire (QoL-AGHDA), was also reduced in KIMS patients. The maintenance dose of GH was significantly higher in patients who were receiving GH prior to enrolment into KIMS (non-naive patients) compared with patients who commenced GH at the time of enrolment (naive patients). In addition, dose of GH correlated significantly with body weight in the former group of patients. Analysis of serum levels of IGF-I indicated that overtreatment with GH was markedly more common in non-naive than in naive patients. The frequency of adverse events in KIMS patients was no higher than that reported in patients receiving placebo in previous clinical trials. Recurrence of pituitary or CNS tumours was reported in six patients, a rate consistent with data from control series. Three deaths were reported, none of which was obviously associated with GH treatment. CONCLUSIONS: Our data, drawn from a large population of hypopituitary adults treated with GH for a total of more than 800 patient years, confirm previous reports that untreated GHD in hypopituitary adults is associated with a number of important clinical problems. In addition, the results suggest that there has been a shift in recent years from determination of GH dose on the basis of body weight to dose titration of individual patients, and indicate that the latter technique has important advantages. The data provide further evidence that GH replacement therapy is well-tolerated in adults. However, it is possible that some adverse events may not become evident over the time scale covered by the present analysis, and continued surveillance therefore remains mandatory.

Adolescent↗

PubMed1999

Budget-holding: the answer to Australian primary care reform?

In common with other Organisation for Economic Cooperation and Development (OECD) countries, Australia is experiencing growth in expenditure on health care. However, while many other nations continue to pursue some variation of managed competition to address these problems, Australia has chosen a more incremental reform path, with initiatives such as the General Practice Strategy, restrictions in doctor supply and coordinated care trials. This article reviews the likely effectiveness of such initiatives in the light of experience and evidence of budget-holding in achieving similar objectives overseas. It concludes that budget-holding offers a more effective strategy than current 'piecemeal' reforms to contain costs and increase efficiency within Australian health care.

Australia↗

PubMed1999

Final height in idiopathic growth hormone deficiency: the KIGS experience. KIGS International Board.

Final height was evaluated in 369 patients with idiopathic growth hormone deficiency (IGHD) enrolled in KIGS--the Pharmacia & Upjohn International Growth Database. At the start of growth hormone (GH) therapy, the patients were 9.8 years of age, their mid-parental height SDS was -0.8, and their height SDS was -3.1. Of the 369 patients, 50% had multiple hormone deficiencies, and puberty was induced in 31%. Patients were 18 years of age at completion of GH therapy, and had received GH at a dose of 0.49 IU/kg/week (0.16 mg/kg/week), with a mean of 5.2 injections/week for 8.1 years. Final height SDS was -1.5, final minus initial height SDS was 1.7 and final minus mid-parental height SDS was -0.5. A Swedish subgroup (n = 69) received conventional GH therapy throughout at 0.65 IU/kg/week (0.22 mg/kg/week), with seven injections/week for a mean of 9.4 years. These patients achieved their genetic potential (final minus mid-parental height SDS, 0.03), with a normal final height SDS of -0.3. For the total group, the following variables were associated with final height: mid-parental height SDS (r = 0.62), injection frequency (r = 0.37), duration of GH treatment (r = 0.28), peak stimulated GH concentration (r = -0.25), age (r = -0.19) (all p < 0.001) and height velocity SDS in the first year of treatment (r = 0.20, p = 0.004). In conclusion, genetic potential, expressed as the mid-parental height, is the variable with the greatest identified influence on final height during GH treatment in IGHD. Current GH regimens will lead to a normal height and attainment of mid-parental height. However, higher dose, individualized GH regimens are likely to be necessary for patients with IGHD who are disadvantaged at the time of commencing GH therapy, such as those with short parents, those whose treatment began in late childhood or adolescence and those with less severe GHD.

Adolescent↗

PubMed1999

Predicting the response to recombinant human growth hormone in Turner syndrome: KIGS models. KIGS International Board. Kabi International Growth Study.

A mathematical model for predicting the growth response in patients with Turner syndrome who received growth hormone (GH) therapy was developed by analysing data from KIGS, the Pharmacia & Upjohn International Growth Database. A model for year 1 of GH therapy explained 46% of the variability of the growth response, with GH dose being the most important of the predictors of height velocity. In years 2-4 of therapy, height velocity during the previous year was the most important predictor, suggesting that an individual's initial response to GH may determine the height outcome of treatment. Additional predictors of height velocity in years 1-4 of GH therapy included age (negative), weight SDS and additional treatment with oxandrolone. The predictions in all 4 years were highly accurate, as indicated by the low error SDs. However, relatively low predictive power (R) during years 2-4 of treatment suggests the models are missing other parameters that would explain more of the variability of the growth response. These growth prediction models could help clinicians to design individualized treatment regimens, provide realistic expectations of therapy outcomes, and adjust treatment on the basis of detected differences between observed and predicted height velocities.

Body Height↗

PubMed1999

A decade of growth hormone treatment in girls with Turner syndrome in the UK. UK KIGS Executive Group.

Fifteen per cent of children treated with growth hormone (GH) are receiving treatment for Turner syndrome, but few results are available on final height in the UK. In this study, data were obtained from the UK KIGS database for 485 girls with Turner syndrome who were treated from 1986, allowing an audit of practice and outcome over 10 years. Over the decade, the mean age of starting growth hormone treatment fell from 10.4 to 8.5 years and the starting dose increased from 0.55 to 0.95 IU/kg/week. The frequency of injections increased from three to six or seven/week. Some girls received suboptimal doses, which also differed depending on whether they were based on weight or surface area. To assess what height gain might be expected at final height, all 52 girls who were prepubertal at the start of treatment, which continued for four years or more, and who had reached final height or had a growth velocity < 2 cm/year were selected. Their mean gain in final height was 5.2 cm and the GH dose was 0.78 IU/kg/week over 5.8 years. Final height gain correlated significantly with duration of treatment, total dose received, and first year response, which itself related to starting dose. This audit shows a changing pattern of treatment over the past decade, which in many instances has been inadequate. When treatment starts before puberty and continues through to final height, with a dose of 30 IU/m2/week in six or seven injections, a mean increase in final height of 5 cm or more would be expected.

Adolescent↗